The candidate's long-term goal is to become expert in the interrogation of cerebral white matter micro- structural integrity and vascular risk assessment as it relates to cognitive functioning in aging. To achieve this goal, the candidate will complete a training program of coursework, workshops and consultations with experts focused on the neuropathology underlying white matter alterations in normal and pathological aging, current and novel neuroimaging techniques for assessing white matter microstructure, vascular risk assessment, cardiovascular disease and its pathophysiology in aging and across minority populations at increased vascular risk. Host institute University of Illinois at Chicago provides training activities and resources relevant to this award including access to seminars, lectures and journal clubs on neuroradiology, vascular neurology, cardiology, and minority research. Primary mentor, Dr. Anand Kumar has performed neuroimaging studies of white matter including the biochemistry of myelin integrity in aging and vascular risk for over 15 years, and has mentored several K awardees and foundation fellowship recipients. He is the Head of the Department of Psychiatry and the recipient of R01s and a K24 to conduct work in late-life depression and vascular risk across the lifespan. The candidate currently contributes to the neuropsychological aspects of this research and is well placed to take advantage of established referral sources and scientific resources for the proposed research. For the proposed research, the candidate will combine a novel MRI technique to interrogate white matter microstructure (i.e., myelin mapping) with the imaging of other white matter pathologies including infarcts and microbleeds to determine the most robust biomarker of vascular risk and cognition in aging and minority populations. While there is a long history of research into the impact of overall white matter damage on the aging brain using currently available neuroimaging methods including diffusion tensor imaging (DTI), they lack sensitivity and specificity as to the contribution of myelin. Given that myelin breakdown begins as early as the fourth decade of life and accelerates with aging, we will perform novel myelin mapping techniques along with current DTI MRI in 60 healthy older adults 60-80 years old (20 Caucasians, 20 African Americans and 20 Hispanic Americans). Pilot data suggests myelin mapping is more sensitive than DTI at quantifying microstructural damage and myelin content in otherwise normal appearing white matter. Older adults will receive comprehensive cognitive and vascular risk assessments. Pilot data suggests a range of vascular risk (elevated in our minority populations) that is associated with cognitive performance, i.e., executive measures. This research stands at the nexus of current and future MRI techniques for identifying and utilizing a biomarker of white matter microstructural integrity in vivo providing a foundation for a new model of vascular aging that may be the basis for specific interventions to slow the progression of white matter damage and associated cognitive decline in aging. PUBLIC HEALTH RELEVANCE: Numerous studies link age-related brain white matter damage and associated vascular risk to cognitive decline and dementia. There is limited information about the underlying microstructural changes driving these white matter alterations in older adults. Given that cardiovascular disease is the leading cause of death and disability in the US, determining ways to identify 'at risk' brain tissue before it is damaged will increase the window o opportunity for preventative measures to slow or stop the progression of cognitive decline and dementia in the aging population.